In the pharmaceutical industry, containers are used for the marketing of drugs. Among the traditionally most used materials is glass tube, as it ensures stability, visibility, endurance, rigidity, moisture resistance, ease of capping, and economy. Such material is appropriate for drugs intended for parenteral administration, which require a sterile container.
The stability of glass containers against the solutions or suspensions that they contain is a quality specification that, among others, characterizes them and is regulated by the guidelines from pharmacopoeias.
The vial or bottle type containers are manufactured from glass tubes, according to processes well-known to those skilled in the art. Thus, the glass tube is loaded into the head of a rotary machine and then, while it is made to spin, the tube is heated to its softening point by a flame and it is pulled along its major axis for elongating and diffusing the portion that has been subjected to the softening by heat to give shape to the desired container.
In these automatic carousel rotary machines, the glass tube is thermally separated in each rotation or cycle, and the process begins at the lower end of the tube. This results in the formation of two closed ends, the lower end of the tube is the one to be discarded in the first cycle, while the upper end is opened again with a flame, and continues to advance to other steps or stations in the same machine to form the mouth of the container that will emerge.
After one cycle, the tube descends abruptly at a point along its vertical height corresponding to the length of a container and is prepared to be heated and pulled by the lower mechanism existing in the machine to separate this lower part completely from the tube and to complete the formation of the bottom of the container; while a part of the tube is separated, its upper part remains again closed, so that it will need to be opened again by means of a burner, so that the operational steps described above are repeated in the glass tube to form in another cycle another mouth for a new container.
Among the disadvantages that the traditional method has, it can be pointed out that, at the moment when the container is manufactured, all the alkaline gases are in constant contact with the inner walls of the tube forming the container, and they adhere to the inner walls thereof, and when it goes through the furnace for the molecular orientation of the glass, these gases initiate the attack to the glass and are difficult to remove with normal washing.
Another disadvantage, consequence from the foregoing, that occurs and is observed in the drug with which the container is filled, results from the attack to the inner walls of the container generating particles originated by the delamination of the glass, that is, silica is released, which is an essential component of glass.
Finally, the major disadvantage involved in the traditional process is the generation of the alkali gases already mentioned above, or of several particles that adhere when handling the glass, so container manufacturers try to eliminate them by injecting to the container a previous treatment such as ammonium sulfate diluted in water, silicone, or hydrofluoric acid to contribute to the removal of these gases and particles at the time of washing the container in the laboratory. It should be noted that an inefficient washing, that does not remove alkali ions, affects the pH changes experienced by the packaged drug, can alter the chemical stability of the drug and, consequently, alters the characteristics of the final product, which may affect its therapeutic activity.
The glass containers for pharmaceutical use, such as bottle, vial or ampoules, are traditionally manufactured under ambient conditions without control or without classification by converting companies; due to the fact that these containers have been considered in the pharmaceutical industry as a packaging material to contain and protect a drug, this pharmaceutical industry with its special facilities needs to set up clean and sterile areas where the necessary equipment is placed to make a previous washing of the container with sterile water for injection.
In the washing process, they are rinsed to remove the particles and free alkali gases generated during the processing of the container, trying to leave the container as clean as possible and ensure the stability of the drug to be stored in it.
Once these containers have been washed, they proceed to a sterilization process by dry heating, to which end a continuous or stationary furnace is usually employed, which normally operates at 240° C. during an average period of 30 minutes, and subsequently the containers move on to another special section also under controlled sterile environments where they will be filled with the corresponding drug, and finally a cap is put in the container, to be transferred to other areas, which are without classification, for its conditioning.
On the other hand, and returning to the manufacture of tubular glass containers performed by converting companies, typically after forming the container (ampoules or vials) it goes through a furnace at 600° C. to temper or align the molecular structure of glass to improve the mechanical resistance of the container, but at the same time it also affects the quality of the container because these areas are generally not clean, the furnaces are of natural gas so they generate carbon monoxide, and the high temperature contributes to fixing the alkaline gases, which were generated from glass during processing, to the surfaces of the container, thereby affecting the hydrolytic resistance of the container. Additionally, the free particles adhere to these walls when the preset temperature is exceeded.
Therefore, it is concluded that with the traditional processes, dirty contaminated containers are produced, which necessarily require a washing and sterilization process, as discussed above.
Traditionally and as a rule, pharmaceutical industry is required to have several systems and areas to manage their products and containers that will be used for the manufacturing or processing a drug. This industry follows the following general steps:
a) Receives a glass container (dirty) vial or ampoule or some other kind of container processed by the converting companies, to be used as primary package for the drug;
b) Washes the containers with the support of special equipment;
c) Sterilizes the container in special furnaces with dry heat at a temperature of 240° C.;
d) With steps b and c, a dirty standard container changes to a sterile container, which is placed in their special machines to perform the filling with the corresponding drug;
e) Transfers his semi-finished product to the conditioning steps for inspection and to put some identification label, or to protect it inside its individual or collective package;
To achieve this, laboratories require an infrastructure to produce, conduct and control water with the aseptic characteristics required, for example, by the Mexican official standard NOM-059-SSA1-2006, to be used in the special machines to rinse the container to eliminate the alkaline gases and dirt residues from the container since this container was manufactured in environmentally non controlled areas.
Besides water, special equipment of high cost is also required, as well as specialized personnel to operate this washing equipment and to control the quality of the water to be used for washing the container, and also investment has to be made in a furnace to dry the container and to sterilize it; these sterilization processes require specialized areas with controls, terminal EPA filters, and special monitoring to document the conditions of this sterilization process and therefore trained personnel for such control and monitoring is also required.
The processes that are currently being implemented do not provide technical solutions that are attractive to the pharmaceutical industry. Sterile containers are proposed by transferring the special equipment and clean facilities that now have the pharmaceutical laboratories to the areas of the converting companies but, in the end, dirty or conventional areas are still being used for the manufacture of the container, gas furnaces are still being used for its molecular orientation and the same equipment used by the pharmaceutical laboratory to wash the container is still being used, as well as a second heating in the furnace to achieve the sterilization.
In this way, no savings are achieved, because the investments are also being moved to the glass converting plant.
The containers continue to require efficient systems for their washing, manufacturers fail to root out the problem of alkalinity of containers.
Thus, there remains a need for a method for preparing glass containers for pharmaceutical use which allows the preparation of said containers with low alkalinity, and that are sterile, and substantially free of particles.